Solution drying system

ABSTRACT

A system for drying chemical reagents on material, particularly for producing product used in making reagent test strips is described. By drying selected chemicals on substrate drawn past a radiant energy source (preferably an IR source), rapid drying may be achieved while obtaining high-quality product. Airflow sufficient to break or disturb a vapor boundary layer above drying solution may be provided to increase drying speeds. Any airflow provided should not disturb the surface of the solution. Still, air-impingement drying techniques may be employed in the system to finish drying reagent material once it is sufficiently dry to be stable in shape. The substrate upon which chemicals are dried may include a reflective coating to facilitate its use with high levels of radiant energy. A metallic or metalized substrate is advantageously used in producing electrochemical test strips. Such test strips may be used in conjunction with various kits and be conveniently read using known hand-held meters.

FIELD OF THE INVENTION

[0001] This invention relates to approaches for drying chemicalcompositions deposited on substrate in solution form. The invention isparticularly suited for drying solution to produce reagent test stripsfor use in analyte determination assays, especially for electrochemicaldetermination of blood analytes.

BACKGROUND OF THE INVENTION

[0002] Analyte detection assays find use in a variety of applicationsincluding clinical laboratory testing, home testing, etc., where theresults of such testing play a prominent role in the diagnosis andmanagement of a variety of conditions. The more common analytes includeglucose, alcohol, formaldehyde, L-glutamic acid, glycerol, galactose,glycated proteins, creatinine, ketone body, ascorbic acid, lactic acid,leucine, malic acid, pyruvic acid, uric acid and steroids, etc. Analytedetection is often performed in connection with physiological fluidssuch as tears, saliva, whole blood and blood-derived products. Inresponse to the growing importance of analyte detection, a variety ofanalyte detection protocols and devices for both clinical and home usehave been developed. Many detection protocols employ a reagent teststrip to detect analyte in a sample.

[0003] As the demand for reagent test strips has grown, the need forevermore efficient and flexible manufacturing approaches has increased.Still, little improvement has been made with respect to the handling ofreagent material incorporated into test strips.

[0004] In producing reagent test strips, a coating of biological reagentwhich usually includes heat labile or moisture sensitive biologicalcomponents (after drying for shelf stability) in a low viscosity aqueoussolution is typically applied to a substrate used to produce one or morestrips. Many existing systems designed to dry such biological reagentsuse high-velocity air impingement techniques to dry coating applied inaqueous form to a substrate. While effective to a certain extent, thereare disadvantages associated with these currently employed techniques,typically due to low heat that may be applied and high air impingementrates necessary for drying in a reasonable amount of time.

[0005] As such, there is great interest in the development of newtechniques for drying a liquid reagent composition with low viscosityand surface tension that has been applied to a substrate. The presentinvention satisfies this need by providing an improved approach todrying a liquid coating or composition applied to a substrate.Specifically, the present invention avoids problems commonly associatedwith high-velocity air impingement drying such as poor efficiency, slowdesiccation, solution disturbance due to airflow. Various features ofthe invention offer increased manufacturing efficiency, a concomitantreduction in manufacturing cost and/or improved test strip quality.Further possible advantages of the present invention may also beapparent to those with skill in the art.

SUMMARY OF THE INVENTION

[0006] The present invention includes devices and methods for dryingsolution, typically having a viscosity less than 100 centipoises (cP),most often around 1.5 cP, that is applied to the surface of a materialor substrate, especially for use in producing reagent test strips.Finished product made using the systems disclosed also form part of theinvention. Typically, the product will be in the form of completereagent test strips. Alternately, test strip precursors including atleast substrate material with chemical solution dried thereon may beregarded as the product of the present invention.

[0007] The invention employs radiant energy to dry solution applied to asubstrate. A non-disturbing airflow may be provided to enhance dryingspeed. Substrate with a chemical coating dried thereon according to thepresent invention may be used in a variety of types of test strips.Preferably, substrate processed according to the present inventionpreferably includes a metallic surface. Such a coating dramaticallyincreases the potential for energy application. Furthermore, a metallicor metal-coated substrate is easily incorporated in electrochemical-typetest strips.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Each of the following figures diagrammatically illustrate aspectsof the present invention. Variation of the invention from that shown inthe figures is contemplated.

[0009]FIG. 1 shows an overview of the inventive system from the frontside.

[0010]FIG. 2 shows a top view of material being coated by a coatersection with solution for drying in an IR dryer section of theinvention.

[0011]FIGS. 3A and 3B shows a bottom and-side views, respectively, of aheating panel used in the IR dryer section.

[0012]FIG. 4 shows a bottom view of a heating panel assembly used in theIR dryer section.

[0013]FIG. 5 shows a close-up of the IR dryer section from the backside.

[0014]FIG. 6 shows product of the inventive system in an intermediatestage of production.

[0015]FIG. 7 shows an exploded perspective view of a test strip madeusing the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0016] In describing the invention in greater detail than provided inthe Summary above, the subject drying system and methods for its use aredescribed first in greater detail, followed by a review of reagent teststrip precursors that can be fabricated with using the subject systemand methods, as well as the test strips produced from the subject teststrip precursors and methods for using these test strips in analytedetection applications.

[0017] Before the present invention is described in such detail,however, it is to be understood that this invention is not limited toparticular variations set forth and may, of course, vary. Variouschanges may be made to the invention described and equivalents may besubstituted without departing from the true spirit and scope of theinvention. In addition, many modifications may be made to adapt aparticular situation, material, composition of matter, process, processstep or steps, to the objective, spirit and scope of the presentinvention. All such modifications are intended to be within the scope ofthe claims made herein. Furthermore, where a range-of values isprovided, it is understood that every intervening value, between theupper and lower limit of that range and any other stated or interveningvalue in that stated range is encompassed within the invention. Theupper and lower limits of these smaller ranges may independently beincluded in the smaller ranges is also encompassed within the invention,subject to any specifically excluded limit in the stated range. Wherethe stated range includes one or both of the limits, ranges excludingeither both of those included limits are also included in the invention.Also, it is contemplated that any optional feature of the inventivevariations described herein may be set forth and claimed independently,or in combination with any one or more of the features described herein.

[0018] Unless defined otherwise, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this invention belongs. Although any methodsand materials similar or equivalent to those described herein can alsobe used in the practice or testing of the present invention, thepreferred methods and materials are now described. All existing subjectmatter mentioned herein (e.g., publications, patents, patentapplications and hardware) is incorporated by reference herein in itsentirety. The referenced items are provided solely for their disclosureprior to the filing date of the present application. Nothing herein isto be construed as an admission that the present invention is notentitled to antedate such material by virtue of prior invention.

[0019] It is noted that as used herein and in the appended claims, thesingular forms “a”, “and”, “said” and “the” include plural referentsunless the context clearly dictates otherwise. Conversely, it iscontemplated that the claims may be so-drafted to exclude any optionalelement. This statement is intended to serve as antecedent basis for useof such exclusive terminology as “solely,” “only” and the like inconnection with the recitation of claim elements or by use of a“negative” limitation

[0020] Turning now to FIG. 1, elements of the present invention areshown in manufacturing system (2). The system shown is a model TM-MC3system produced by Hirano Tecseed Co. Ltd (Nara, Japan) adapted for usein the present invention. Preferably, it includes such solution coatingfeatures in a coating section (4) as described in U.S. patentapplication, titled “Solution Striping System,” to the inventors of thepresent system, filed on even date herewith.

[0021]FIG. 2 shows a top view of features of the coating systempreferably used in connection with the radiant energy drying system orsection (6). In FIG. 2, a substrate or webbing material (8) is beingcoated which solution (10) fed to a die (12) by one or more pumps (14)to be deposited in the form of stripes or bands. A backing roller (16)is used to locate the webbing as it advances past the die in thedirection indicated by the bold arrows.

[0022] As shown in FIG. 1, substrate (8) is provided in the form of aweb by way of supply reel (18) and substrate with a reagent coatingthereon is accumulated on a take-up real (20) after passing variousguide rollers and passing through dryer section (6). One or moreauxiliary dryer sections (22) may be provided in-line with dryer section(6) as well. These may include features like those in dryer section (6)or employ air-impingement drying techniques.

[0023] Preferably, the various dryer sections are provided behind acover or within a housing as shown. Door(s) may be included for access.When employed in a radiant drier section, the structure will provide ashield from unnecessary exposure to radiant energy and act like thewalls of an oven, re-radiating absorbed energy and speeding dryingwithin. When employed in auxiliary dryer sections utilizing forced airfor drying (especially, heated forced air), the structure provides acontainment environment.

[0024] Substrate or webbing (8) preferably comprises a semi-rigidmaterial that is capable of providing structural support to a test stripin which it may be incorporated. The substrate may comprise an inertmaterial like a plastic (e.g., PET, PETG, polyimide, polycarbonate,polystyrene or silicon), ceramic, glass, paper, or plastic-paperlaminate.

[0025] For use in an electrochemical test strip, at least the surface ofthe substrate that faces a reaction area in the strip will comprise ametal, where metals of interest include palladium, gold, platinum,silver, iridium, carbon, doped indium tin oxide, stainless steel andvarious alloys of these metals. In many embodiments, a noble metal suchas gold, platinum or palladium is used.

[0026] In some instances, the substrate itself may be made of metal,especially one of those noted above. It is generally preferred, however,that the substrate comprise a composite of a support coated with ametallic and/or conductive coating (such as palladium, gold, platinum,silver, iridium, carbon conductive carbon ink doped tin oxide orstainless steel). For further discussion of substrate or supportmaterials that find use in certain embodiments of the subject invention,see U.S. Pat. No. 4,935,346 titled “Minimum Procedure System for theDetermination of Analytes” issued Jun. 19, 1990 to Roger Phillips et al.and U.S. Pat. No. 5,304,468 titled “Reagent Test Strip and Apparatus forDetermination of Blood Glucose” issued Apr. 19, 1994 to Roger Phillipset al.

[0027] When a metal-coated support is to be employed as the substrate orwebbing material (8), its thickness will typically range from about0.002 to 0.014 in (51 to 356 μm), usually from about 0.004 to 0.007 in(102 to 178 μm), while the thickness of the metal layer will typicallyrange from about 10 to 300 μm and usually from about 20 to 40 nm. A goldor palladium coating may be preferred for this purpose. For ease ofmanufacture, it may be preferred that the entire surface of substrate(8) is coated with metal.

[0028] Whatever the type substrate used, the subject systems and methodsmay be employed to dry a variety of different types of coatingcompositions applied to the surface of a substrate. In many embodiments,coating (10) comprises one or more reagent members of a signal producingsystem. A “signal producing system” is one in which one or more reagentswork in combination to provide a detectable signal in the presence of ananalyte that can be used to determine the presence and/or concentrationof analyte. The signal producing system may be a signal producing systemthat produces a color that can be related to the presence orconcentration of an analyte or it may be a signal producing system thatproduces an electrical current that can be related to the presence orconcentration of an analyte. Other types of systems may be used as well.

[0029] A variety of different color signal producing systems are known.Representative color signal producing systems of interest includeanalyte oxidation signal producing systems. An “analyte oxidation signalproducing system” is one that generates a detectable calorimetric signalfrom which the analyte concentration in the sample is derived, theanalyte being oxidized by a suitable enzyme to produce an oxidized formof the analyte and a corresponding or proportional amount of hydrogenperoxide. The hydrogen peroxide is then employed, in turn, to generatethe detectable product from one or more indicator compounds, where theamount of detectable product produced by the signal producing system,(i.e. the signal) is then related to the amount of analyte in theinitial sample. As such, the analyte oxidation signal producing systemsuseable in the subject test strips may also be correctly characterizedas hydrogen peroxide based signal producing systems.

[0030] As indicated above, the hydrogen peroxide based signal producingsystems include an enzyme that oxidizes the analyte and produces acorresponding amount of hydrogen peroxide, where by corresponding amountis meant that the amount of hydrogen peroxide that is produced isproportional to the amount of analyte present in the sample. Thespecific nature of this first enzyme necessarily depends on the natureof the analyte being assayed but is generally an oxidase. As such, thefirst enzyme may be: glucose oxidase (where the analyte is glucose);cholesterol oxidase (where the analyte is cholesterol); alcohol oxidase(where the analyte is alcohol); lactate oxidase (where the analyte islactate) and the like. Other oxidizing enzymes for use with these andother analytes of interest are known to those of skill in the art andmay be employed. In those embodiments where the reagent test strip isdesigned for the detection of glucose concentration, the first enzyme isglucose oxidase. The glucose oxidase may be obtained from any convenientsource (e.g., a naturally occurring source such as Aspergillus niger orPenicillum), or be recombinantly produced.

[0031] The second enzyme of the signal producing system is an enzymethat catalyzes the-conversion of one or more indicator compounds into adetectable product in the presence of hydrogen peroxide, where theamount of detectable product that is produced by this reaction isproportional to the amount of hydrogen peroxide that is present. Thissecond enzyme is generally a peroxidase, where suitable peroxidasesinclude: horseradish peroxidase (HRP), soy peroxidase, recombinantlyproduced peroxidase and synthetic analogs having peroxidative activityand the like. See e.g., Y. Ci, F. Wang; Analytica Chimica Acta, 233(1990), 299-302.

[0032] The indicator compound or compounds are ones that are eitherformed or decomposed by the hydrogen peroxide in the presence of theperoxidase to produce an indicator dye that absorbs light in apredetermined wavelength range. Preferably, the indicator dye absorbsstrongly at a wavelength different from that at which the sample or thetesting reagent absorbs strongly. The oxidized form of the indicator maybe the colored, faintly-colored, or colorless final product thatevidences a change in color. That is to say, the testing reagent canindicate the presence of analyte (e.g., glucose) in a sample by acolored area being bleached or, alternatively, by a colorless areadeveloping color.

[0033] Indicator compounds that are useful in the present inventioninclude both one- and two-component calorimetric substrates.One-component systems include aromatic amines, aromatic alcohols,azines, and benzidines, such as tetramethyl benzidine-HCl. Suitabletwo-component systems include those in which one component is MBTH, anMBTH derivative (see for example those disclosed in U.S. patentapplication Ser. No. 08/302,575, titled “incorporated herein byreference), or 4-aminoantipyrine and the other component is an aromaticamine, aromatic alcohol, conjugated amine, conjugated alcohol oraromatic or aliphatic aldehyde. Exemplary two-component systems are3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) combinedwith 3-dimethylaminobenzoic acid (DMAB); MBTH combined with3,5-dichloro-2-hydroxybenzene-sulfonic acid (DCHBS); and3-methyl-2-benzothiazolinone hydrazone N-sulfonyl benzenesulfonatemonosodium (MBTHSB) combined with 8-anilino-1 naphthalene sulfonic acidammonium (ANS). In certain embodiments, the dye couple MBTHSB-ANS ispreferred.

[0034] Signal producing systems that produce a fluorescent detectableproduct (or detectable non-fluorescent substance, e.g. in a fluorescentbackground) may also be employed in the invention, such as thosedescribed in: Kiyoshi Zaitsu, Yosuke Ohkura, New fluorogenic substratesfor Horseradish Peroxidase: rapid and sensitive assay for hydrogenperoxide and the Peroxidase. Analytical Biochemistry (1980) 109,109-113.

[0035] Signal producing systems that produce an electric current (e.g.,as are employed in electrochemical test strips) are of particularinterest to the present invention. Such reagent systems include redoxreagent systems, which reagent systems provide for the species that ismeasured by the electrode and therefore is used to derive theconcentration of analyte in a physiological sample. The redox reagentsystem present in the reaction area typically includes at leastenzyme(s) and a mediator. In many embodiments, the enzyme member(s) ofthe redox reagent system is an enzyme or plurality of enzymes that workin concert to oxidize the analyte of interest. In other words, theenzyme component of the redox reagent system is made up of a singleanalyte oxidizing enzyme or a collection of two or more enzymes thatwork in concert to oxidize the analyte of interest. Enzymes of interestinclude oxidases, dehydrogenases, lipases, kinases, diphorases,quinoproteins, and the like.

[0036] The specific enzyme present in the reaction area depends on theparticular analyte for which the electrochemical test strip is designedto detect, where representative enzymes include: glucose oxidase,glucose dehydrogenase, cholesterol esterase, cholesterol oxidase,lipoprotein lipase, glycerol kinase, glycerol-3-phosphate oxidase,lactate oxidase, lactate dehydrogenase, pyruvate oxidase, alcoholoxidase, bilirubin oxidase, uricase, and the like. In many preferredembodiments where the analyte of interest is glucose, the enzymecomponent of the redox reagent system is a glucose oxidizing enzyme,e.g. a glucose oxidase or glucose dehydrogenase.

[0037] The second component of the redox reagent system is a mediatorcomponent, which is made up of one or more mediator agents. A variety ofdifferent mediator agents are known in the art and include:ferricyanide, phenazine ethosulphate, phenazine methosulfate,phenylenediamine, 1-methoxy-phenazine methosulfate,2,6-dimethyl-1,4-benzoquinone, 2,5-dichloro-1,4-benzoquinone, ferrocenederivatives, osmium bipyridyl complexes, ruthenium complexes, and thelike. In those embodiments where glucose in the analyte of interest andglucose oxidase or glucose dehydrogenase are the enzyme components,mediators of particular interest are ferricyanide, and the like.

[0038] Other reagents that may be present in the reaction area includebuffering agents, citraconate, citrate, malic, maleic, phosphate, “Good”buffers and the like. Yet other agents that may be present include:divalent cations such as calcium chloride, and magnesium chloride;pyrroloquinoline quinone; types of surfactants such as Triton, Macol,Tetronic, Silwet, Zonyl, and Pluronic; stabilizing agents such asalbumin, sucrose, trehalose, mannitol, and lactose.

[0039] For use in producing electrochemical test strips, a redox systemincluding at least an enzyme and a mediator as described above ispreferably used for coating (10). In solution, the system preferablycomprises a mixture of about 6% protein, about 30% salts and about 64%water. The fluid most preferably has a viscosity of roughly 1.5 Cp.Still, it is to be understood that numerous kinds of solution may bedried with the inventive system. Most preferably, the solution comprisesreagent-type solution. Indeed, the advantages of the present system aremost apparent in connection with drying solution in which chemicalactivity must be maintained and with less viscous solutions,particularly solutions with a viscosity below 100 Cp.

[0040] As for hardware to be used in the inventive system, FIGS. 3A and3B show a preferred heating element used to deliver radiant energywithin dryer section (6). The apparatus depicted is a panel or heaterboard (24) produced by Radiant Energy Systems (Wayne, N.Y.). For eachboard (24), 8 resistive heaters (26) are provided in connection with aceramic thermowell (28) and associated electrical connections (30). Theheaters are set to emit medium wavelength infrared energy. Instead ofusing one or more heater panels (24), a number of discrete heaters maybe provided in succession. A suitable industrial-type infrared dryingunit is also produced by Radiant Energy Systems as model number SFA-24.Alternately, one or more quartz tube heaters may be used to provideradiant (especially IR) energy for drying solution on webbing accordingto the present invention. A Sun-Mite™ heater model number FFH-912B byFostoria (Comstock, Mich.) has proved effective in this regard.

[0041]FIG. 4 shows a most preferred arrangement for heater elements.Three heater boards (24) are shown in series. Screens (32) are providedin front of the heater elements. When employing medium-wavelengthinfrared energy as preferred, the screens will have serve to rays,randomizing and making the energy application more even.

[0042]FIG. 5 shows the apparatus in FIG. 4 in place within dryingsection (6). While six heater boards (24) are shown, energy ispreferably only applied by elements above webbing (8) moving asindicated by the in-line arrows. Heater elements (26) are preferablypositioned at a height between about 1 and 5 inches (25.4 and 127 mm)above the substrate upon which a coating has been deposited. Morepreferably, the spacing is between about 2 and 4 inches (50.8 and 101.6mm). The amount of energy applied along webbing or substrate (8) ispreferably between about 3.5 and 8 watts per square inch.

[0043] It is especially feasible to apply such high amounts of energyalong the webbing when the webbing includes a surface that reflects muchof the impinging. Using a reflective coating having a low emissivitysuch as platinum or palladium (about 0.1), high energy levels do notdestroy the substrate. In some instances, it may be possible to use asubstrate that transmits or is transparent to the energy and achieve thesame effect.

[0044] In either event, solution (10) will typically easily absorbenergy, i.e., have a high emissiviy (about 0.9). Accordingly, the IRenergy applied has an effect where needed for drying, but not elsewhere.

[0045] Even under high-intensity drying conditions according to thepresent invention, it is possible to dry reagent coating withoutsignificantly affecting reagent activity. For instance, whereprotein-based reagents are included in the coating, the dryingconditions employed are set so as not to denature the protein reagentsbeyond utility. More particularly, when the solution applied to thesurface of the substrate includes an enzyme, activity of the enzymaticcoating composition following drying by the present does not exhibitsignificant loss of activity as determined by DCIP/PMS methodology. Thelow absorptivity of the water in the coating and the effect ofevaporative cooling on the solution upon water volatilization protectthe proteins from denaturing.

[0046] While the latter effect would have some utility in drying withheated air alone, the other advantages applicable to drying with radiantenergy are not present. Attempting rapid drying by air impingementtechniques in effort to obtain the performance available with thepresent system would simply destroy the reagent coating activity or meltthe webbing.

[0047] In the present invention, one or more temperature sensors (34)may be provided within dryer (6). Thermocouples and/or IR sensors may beemployed. They may be used to monitor the ambient or air temperaturewithin drying section or the temperature of the webbing. Even withreflective coating on the webbing having a high reflectance or lowemissivity, the plastic upon which the coating is often applied(preferably polyester web) may be affected by temperatures above about300° F. (150° C.). Feedback from the temperature sensors may be used toset or adjust dryer temperature to avoid damaging the webbing or reagentmaterial coated thereon.

[0048] With the present invention, webbing processing speeds (i.e., therate at which solution may be dried upon substrate) as high as 100 ftper minute may be achieved. More typically, processing speeds between 5and 25-50 feet of substrate per minute are realized. The highestproduction speeds are available in connection with a setup in which theheater element(s) are used in connection one or more fans (36) thatprovide a non-disturbing airflow to break the vapor barrier of thesolution being dried within radiant dryer section (6).

[0049] As noted above,,one or more optional auxiliary dryer sections(22) may be used in the present invention. Typically, each comprises anair impingement dryer utilizing heated, forced air. Auxiliary dryers(22) are useful in speeding-up web processing by completing drying oncethe shape of the bead of solution laid-down on the substrate issubstantially set by radiant-energy drying.

[0050] Normally, air impingement drying introduces a host of problems,especially in drying low viscosity solution. Simple air-impingementdrying introduces both cross-web and down-web reagent stripeinconsistency as compared to the processes of the present invention.

[0051] At the most basic level, it is easily understood howhigh-velocity air impinging upon solution produces ripples, resulting inan uneven dried product along the length of a stripe of solution. Theeffect on the cross-section of dried reagent produced usingair-impingement drying alone is, however, less obvious. Solution coatingdried merely by air-impingement techniques exhibits an exaggeratedU-shaped cross-section. Such a profile develops due to migration byosmosis of reagent over time toward edges that dry more rapidly.

[0052] As evidenced by improved consistency in reagent test strips madewith reagent coating dried according to the present invention, a moreuniform cross section results utilizing radiant energy. It is believedthat the rapid drying potential offered by the present inventionalleviates edge build-up by decreasing the available time for migrationby osmosis to occur.

[0053] Also, down-web consistency is improved since solution is notdisturbed when it is prone to movement. Even when auxiliaryair-impingement dryers (22) are used in system (2), ripples ordisturbances are not evident in dried reagent coating since the radiantsection (6) applies sufficient energy to effectively set the shape ofthe coating.

[0054] Rapid shape setting with radiant energy also helps produceconsistent product in another regard. When employing low viscosity orlow surface tension solution with substrate that is hydrophilic orincludes a hydrophilic coating (as may often be preferred in anelectrochemical test strip, see U.S. patent application Ser. No.09/497,269 titled, “Electrochemical Test Strip for Use in AnalyteDetermination” and U.S. Patent Application, titled “Solution StripingSystem”), the solution has a tendency to “wet-out” the substraterapidly. Solution will tend to flow across and coat more area thandesired, rather than maintaining a stripe or a bead upon application.The immediate drying effect achieved by the present invention byapplying radiant energy at sufficient levels halts this, setting theboundaries of the reagent. Accordingly, costly reagent is not lost bymigration. This approach offers significant improvement in dried stripewidth accuracy and placement precision.

[0055] Furthermore, thicker coating regions of reagent may be achievedwithout requiring multiple coats of solution. In instances where it isnot feasible to alter the surface tension of reagent or the surfaceenergy of substrate to be coated, there are few alternatives to controlstripe width and thickness. The ability to rapidly set the shape ofthick coatings makes their application feasible.

[0056] In an electrochemical test strip, the dried reagent coatingserves as an active layer in the electrochemical cell. Sufficientconcentrations of the reagent components are required to achievesatisfactory results. It has been appreciated by the inventors hereofthat low concentrations of reagent produce poor test results. Theability to apply relatively thicker reagent coating on substrate forinclusion in test strips thus offers potential for improved test stripaccuracy.

[0057] Various forms of product may be produced in utilizing features ofthe invention. FIG. 6 shows a test strip precursor (54) in card formaking electrochemical test strips. It comprises substrate or webbingmaterial (8) as shown in FIG. 4 cut in two between the reagent stripesto form two 2⅛ in (5.4 cm) wide cards further modified with notches (56)as shown. The precursor may further comprise an opposing webbing (58)and a spacer (60) therebetween. Each are shown as cut, punched, orstamped to define test strip ends (62).

[0058] A continuous process (e.g., one in which various rolls ofmaterial are brought together to produce the precursor) such as in acontinuous web process, or a discontinuous process (e.g., one in whichthe strip portions are first cut and then joined to each other) may beemployed working with the precursor pieces. Other modes ofmultiple-component strip fabrication may also be employed.

[0059] The spacer preferably comprises a double-stick adhesive product.It may be fabricated from any convenient material, where representativematerials include PET, PETG, polyimide, polycarbonate and the like.Webbing (8) is preferably plastic with sputtered-on palladium andfunctions as a “working” electrode, while webbing (58) is preferablygold coated plastic and functions as a “reference” electrode. Eachwebbing portion may have a thickness ranging from about 0.005 to 0.010in (127 μm to 254 μm).

[0060] The test strip precursor may be in the form of a continuous tapeor be in the form of a basic card (e.g., a parallelogram or analogousshape of shorter length) prior to the production stage shown in FIG. 6.As such, the length of the test strip precursor may vary considerably,depending on whether it is in the form of a tape or has a shorter shape(i.e., in the form of a card). The width of the test strip precursor mayalso vary depending on the nature of the particular test strip to bemanufactured. In general, the width of the test strip precursor (orcoated substrate alone) may range from about 0.5 to 4.5 in (13 to 114mm). It may, of course, be wider, especially to accommodate additionalstripes of solution.

[0061] As alluded to above, the width and depth of solution coatingapplied to substrate or webbing (8) may also vary depending on thenature of the product to be manufactured. For test strip production, thestriping width will typically range from about 0.05 to 0.5 in (1.3 to 13mm) and its thickness range from about 5 to 50 microns.

[0062] Especially for use in electrochemical test strips, stripes orbands of aqueous reagent material are most preferably laid down inwidths about 0.065 to 0.200 in (1.7 to 5.1 mm) wide and between about 15and 25 microns deep when wet.

[0063] After being cut into a card, like that shown in FIG. 6, precursor(54) is singulated to produce individual test strips (62). Like theprecursor, test strips may be cut manually or by automated means (e.g,with a laser singulation means, a rotary die cutting means, etc.). Theprecursor may be cut in stages as shown and described, or in a singleoperation. Patterns used for cutting may be set by a program, guide,map, image, or other direction means that directs or indicates how thetest strip precursor should be cut into the reagent test strips. Thepattern may or may not be visual on the test strip blank prior tocutting/singulation. Where the pattern is visible, the image may beapparent from a complete outline, a partial outline, designated pointsor markings of a strip. For further details as to how test strips may bemanufactured, see U.S. patent application Ser. No. 09/737,179 titled“Method of Manufacturing Reagent Test Strips.”

[0064]FIG. 7 shows an exploded view of a single representativeelectrochemical test strip (62). The subject test trip comprising areference electrode (64) and working electrode (66) separated by spacermember (60) which is cut away to define a reaction zone or area (68) incommunication with side ports (70) defined by a break in the spacer'scoverage adjacent reagent patch (72) formed from a dried solutionstripe.

[0065] To use such an electrochemical test strip, an aqueous liquidsample (e.g., blood) is placed into the reaction zone. The amount ofphysiological sample that is introduced into the reaction area of thetest strip may vary, but generally ranges from about 0.1 to 10 μl,usually from about 0.3 to 0.6 μl. The sample may be introduced into thereaction area using any convenient protocol, where the sample may beinjected into the reaction area, allowed to wick into the reaction area,or be otherwise introduced through the ports.

[0066] The component to be analyzed is allowed to react with the redoxreagent coating to form an oxidizable (or reducible) substance in anamount corresponding to the concentration of the component to beanalysed (i.e., analyte). The quantity of the oxidizable (or reducible)substance present is then estimated by an electrochemical measurement.

[0067] The measurement that is made may vary depending on the particularnature of the assay and the device with which the electrochemical teststrip is employed (e.g., depending on whether the assay is coulometric,amperometric or potentiometric). Measurement with the strip (62) ispreferably accomplished by way of a meter probe element inserted betweenthe electrode members to contact their respective interior surfaces.Usually, measurement is taken over a given period of time followingsample introduction into the reaction area. Methods for makingelectrochemical measurements are further described in U.S. Pat. Nos.4,224,125; 4,545,382; and 5,266,179; as well as WO 97/18465 and WO99/49307 publications.

[0068] Following detection of the electrochemical signal generated inthe reaction zone, the amount of the analyte present in the sample istypically determined by relating the electrochemical signal generatedfrom a series of previously obtained control or standard values. In manyembodiments, the electrochemical signal measurement steps and analyteconcentration derivation steps, are performed automatically by a devicedesigned to work with the test strip to produce a value of analyteconcentration in a sample applied to the test strip. A representativereading device for automatically practicing these steps, such that userneed only apply sample to the reaction zone and then read the finalanalyte concentration result from the device, is further described incopending U.S. application Ser. No. 09/333,793 filed Jun. 15, 1999.

[0069] The reaction zone in which activity occurs preferably has avolume of at least about 0.1 μl, usually at least about 0.3 μl and moreusually at least about 0.6 μl, where the volume may be as large as 10 μlor larger. The size of the zone is largely determined by thecharacteristics of spacer (60). While the spacer layer is shown todefine a rectangular reaction area in which the aforementioned activityoccurs, other configurations are possible, (e.g, square, triangular,circular, irregular-shaped reaction areas, etc.). The thickness of thespacer layer generally ranges from about 0.001 to 0.020 in (25 to 500μm), usually from about 0.003 to 0.005 in (76 to 127 μm). The manner inwhich the spacer is cut also determines the characteristics of ports(70). The cross-sectional area of the inlet and outlet ports may vary aslong as it is sufficiently large to provide an effective entrance orexit of fluid from the reaction area.

[0070] As depicted, the working and reference electrodes are generallyconfigured in the form of elongate strips. Typically, the length of theelectrodes ranges from about 0.75 to 2 in (1.9 to 5.1 cm), usually fromabout 0.79 to 1.1 in (2.0 to 2.8 cm). The width of the electrodes rangesfrom about 0.15 to 0.30 in (0.38 to 0.76 cm), usually from about 0.20 to0.27 in (0.51 to 0.67 cm). In certain embodiments, the length of one ofthe electrodes is shorter than the other, wherein in certain embodimentsit is about 0.135 in (3.5 mm) shorter. Preferably, electrode and spacerwidth is matched where the elements overlap. In a most preferredembodiment, electrode (64) is 1.365 in (35 cm) long, electrode (66) is1.5 in (3.8 cm) long, and each are 0.25 in (6.4 mm) wide at theirmaximum and 0.103 in (2.6 mm) wide at their minimum, reaction zone (68)and ports (70) are 0.065 in (1.65 mm) wide and the reaction zone has anarea of about 0.0064 in² (0.041 cm²). The electrodes typically have athickness ranging from about 10 to 100 nm, preferably between about 18to 22 nm. The spacer incorporated in the strip is set back 0.3 in (7.6mm) from the end electrode (66), leaving an opening between theelectrodes that is 0.165 in (4.2 mm) deep.

[0071] Test strips according to the present invention may be provided inpackaged combination with means for obtaining a physiological sampleand/or a meter or reading instrument such as noted above. Where thephysiological sample to be tested by a strip is blood, the subject kitsmay include a tool such as a lance for sticking a finger, a lanceactuation means, and the like. Further, test strip kits may include acontrol solution or standard (e.g., a glucose control solution thatcontains a standardized concentration of glucose). Finally, a kit mayinclude instructions for using test strips according to the invention inthe determination of an analyte concentration in a physiological sample.These instructions may be present on one or more of container(s),packaging, a label insert or the like associated with the subject teststrips:

[0072] Though the invention has been described in reference to a singleexample, optionally incorporating various features, the invention is notto be limited to the set-up described. The invention is not limited tothe uses noted or by way of the exemplary description provided herein.It is to be understood that the breadth of the present invention is tobe limited only by the literal or equitable scope of the followingclaims.

That being said, we claim:
 1. A method of producing reagent coatedsubstrate comprising: coating substrate with reagent in solution, andexposing said solution to radiant energy provided by at least oneradiant energy heater.
 2. The method of claim 1, wherein airflowsufficient only to break a vapor barrier of the solution is directed atsaid solution while exposed to radiant energy.
 3. The method of claim 1,wherein said substrate is provided in a roll, and is fed past saidenergy source.
 4. The method of claim 1, wherein said reagent isprovided in at least one stripe.
 5. The method of claim 1; wherein saidsubstrate includes a reflective surface.
 6. The method of claim 5,wherein said feeding of said substrate is performed at a rate betweenabout 5 and 50 feet per minute.
 7. The method of claim 5, wherein saidradiant energy is infrared energy delivered at an intensity of at least3.5 W/in².
 8. A reagent coated substrate made by the process of claim 1,whereby dried reagent having a substantially uniform thickness isproduced.
 9. The reagent coated substrate of claim 8, wherein saidsubstrate comprises an inert backing material and a metallic coating.10. The reagent coated substrate of claim 8, in a test strip precursor.11. The reagent coated substrate of claim 8, in a reagent test strip.12. The reagent coated substrate of claim 8, in an electrochemical-typetest strip.
 13. The reagent coated substrate of claim 8, in anelectrochemical-type test strip comprising a pair of electrodes and aspacer therebetween defining a reaction zone.
 14. The reagent coatedsubstrate of claim 8, in a reagent test strip wherein said reagent teststrip can be read by a hand held meter.
 15. A system for use indetermining the concentration of an analyte in a physiological sample,comprising: a reagent test strip comprising substrate as described inclaim 8 in combination with a hand-held meter, wherein said reagent teststrip and said meter are adapted to interface with one another.
 16. Thesystem of claim 15, wherein said reagent test strip is received by saidmeter.
 17. A kit for use in determining the concentration of an analytein a physiological sample, comprising: a reagent test strip comprisingsubstrate as described in claim 8 in packaged combination with at leastone of a set of directions for test strip use, a means for obtaining aphysiological sample, and an analyte standard.
 18. A method fordetermining the concentration of an analyte in a sample, said methodcomprising: applying a fluid sample to a reagent test strip comprising areagent coated substrate as described in claim 8; detecting a signalfrom said reagent test strip; and relating said detected signal to theconcentration of analyte in said sample to determine the concentrationof said analyte in said fluid sample.
 19. The method of claim 18,wherein said fluid sample is a biological sample.
 20. The method ofclaim 18, wherein said analyte is glucose.
 21. The method of claim 18,wherein said detecting and relating steps are performed by a hand heldmeter.